Breast milk oligosaccharides: what do we know today?

Cover Page

Cite item

Full Text

Abstract

Breastfeeding remains the "gold standard" for feeding babies in the first year of life. Breast milk contains a mixture of nutrients; their amount varies throughout the lactation period and even throughout the day. The composition of breast milk (BM) is complex and dynamic. Currently, BM oligosaccharides (BMOs) are of most interest to researchers. Due to advances in science and biotechnology, more than 200 BMOs have been identified. Human BM is the richest source of oligosaccharides among all mammals (for instance, their content in cow's milk is almost 1,000 times lower). Numerous favorable effects of BMOs on child health are related to the immune response, gut barrier function, and protection against pathogens. BMOs as prebiotics contribute to the formation of the infant's intestinal microbiome. The BM contains a complex bacterial community whose composition depends on the maternal microbiome (skin, gut, genital, urethral tracts) that forms the infant gut microbial community. In the absence of breastfeeding, modern formulas can be used; BMOs in their composition make them more like BM.

Full Text

Restricted Access

About the authors

Irina N. Zakharova

Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: zakharova-rmapo@yandex.ru
ORCID iD: 0000-0003-4200-4598

D. Sci. (Med.), Prof.

Russian Federation, Moscow

Iana V. Orobinskaia

Russian Medical Academy of Continuous Professional Education; Khimki Regional Hospital

Email: zakharova-rmapo@yandex.ru

Resident

Russian Federation, Moscow; Khimki

Narine G. Sugian

Russian Medical Academy of Continuous Professional Education; Khimki Regional Hospital

Email: zakharova-rmapo@yandex.ru

Cand. Sci. (Med.)

Russian Federation, Moscow; Khimki

Tatiana A. Kovtun

PROGRESS

Email: zakharova-rmapo@yandex.ru
ORCID iD: 0000-0002-0303-6899

Cand. Sci. (Med.)

Russian Federation

Elena V. Tabulovich

PROGRESS

Email: zakharova-rmapo@yandex.ru

staff member

Russian Federation

References

  1. Захарова И.Н., Дмитриева Ю.А., Ягодкин M.В. Олигосахариды грудного молока: еще один шаг на пути приближения детских молочных смесей к «золотому стандарту» вскармливания ребенка. Медицинский совет. 2018;17:30-7 [Zakharova IN, Dmitrieva YuA, Yagodkin MV. Breast milk oligosaccharides: one more step on the path to making infant formulas more like a “gold standard” for infant feeding. Meditsinskiy sovet. 2018;17:30-7 (in Russian)].
  2. Westerfield KL, Koenig K, Oh R. Breastfeeding: Common Questions and Answers. Am Fam Phys. 2018;98:368-73.
  3. Bagci Bosi AT, Eriksen KG, Sobko T, et al. Breastfeeding Practices and Policies in WHO European Region Member States. Public Health Nutr. 2016;19:753-64.
  4. Davanzo R, Moro G, Sandri F, et al. Breastfeeding and Coronavirus Disease-2019: Ad Interim Indications of the Italian Society of Neonatology Endorsed by the Union of European Neonatal & Perinatal Societies. Matern Child Nutr. 2020;16:e13010.
  5. Fernández-Carrasco FJ, Vázquez-Lara JM, González-Mey U, et al. Coronavirus Covid-19 Infection and Breastfeeding: An Exploratory Review. Available at: https://pubmed.ncbi.nlm.nih.gov/ 32458823. Accessed: 20.09.2020.
  6. Berger B, Porta N, Foata F, et al. Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics. mBio. 2020;11(2):e03196-19. doi: 10.1128/mBio.03196-19; PMID: 32184252; PMCID: PMC7078481
  7. Santos FS, Santos FCS, Santos LH, et al. Breastfeeding and Protection against Diarrhea: An Integrative Review of Literature. Einstein. 2015;13(3):435-40. doi: 10.1590/S1679-45082015RW3107
  8. Engfer MB, Stahl B, Finke B, et al. Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am J Clin Nutr. 2000;71(6):1589-96.
  9. Kunz C. Historical Aspects of Human Milk Oligosaccharides. Adv Nutr. 2012;3(3):430S-9S.
  10. Hauser J, Pisa E, Arias Vasquez A, et al. Sialylated human milk oligosaccharides program cognitive developmentthrough a non-genomic transmission mode. Mol Psychiatry. 2021;26:2854-71. doi: 10.1038/s41380-021-01054-9
  11. Макарова Е.Г., Нетребенко О.К., Украинцев С.Е. Олигосахариды грудного молока: история открытия, структура и защитные функции. Педиатрия им. Г.Н. Сперанского. 2018;97(4):152-60 [Makarova EG, Netrebenko OK, Ukraintsev SE. Breast milk oligosaccharides: the history of discovery, structure and protective functions. Pediatria n.a. GN Speransky. 2018;97(4):152-60 (in Russian)].
  12. Кottler R, Mank M, Hennig R, et al. Development of a high-throughput glycoanalysis method for the characterization of oligosaccharides in human milk utilizing multiplexed capillary gel electrophoresis with laser-induced fluorescence detection. Electrophoresis. 2013;34:2323-36.
  13. Thurl S, Munzert M, Boehm G, et al. Systematic review of the concentrations of oligosaccharides in human milk. Nutr Rev. 2017;75(11):920-33. doi: 10.1093/nutrit/nux044; PMID: 29053807; PMCID: PMC5914348
  14. Morozov V, Hansman G, Hanisch FG, et al. Human milk oligosaccharides as promisingantivirals. Mol Nutr Food Res. 2018;62:e1700679
  15. Kunz C, Kuntz S, Rudloff S. Bioactivity of humanmilk oligosaccharides. In: Food Oligosaccharides: Production, Analysis and Bioactivity. Eds FM Moreno, ML Sanz. 1st ed. Hoboken: John Wiley & Sons, Ltd., 2014.
  16. Bering SB. Human Milk Oligosaccharides to Prevent Gut Dysfunction and Necrotizing Enterocolitis in Preterm Neonates. Nutrients. 2018;10:1461.
  17. Sprenger GA, Baumgärtner F, Albermann C. Production of Human Milk Oligosaccharides by Enzymatic and Whole-Cell Microbial Biotransformations. J Biotechnol. 2017;258:79-91.
  18. Moubareck CA. Human Milk Microbiota and Oligosaccharides: A Glimpse into Benefits, Diversity, and Correlations. Nutrients. 2021;13(4):1123.
  19. Plaza-Díaz J, Fontana L, Gil A. Human Milk Oligosaccharides and Immune System Development. Nutrients. 2018;10(8):1038. doi: 10.3390/nu10081038; PMID: 30096792; PMCID: PMC6116142
  20. Bode L, Jantscher-Krenn E. Structure-Function Relationships of Human Milk Oligosaccharides. Adv Nutr. 2012;3:383S-91S.
  21. McGuire MK, Meehan CL, McGuire MA, et al. What’s Normal? Oligosaccharide Concentrations and Profiles in Milk Produced by Healthy Women Vary Geographically. Am J Clin Nutr. 2017;105:1086-100.
  22. Kunz C, Meyer C, Collado MC, et al. Influence of gestational age, secretor, and Lewis blood group status on the oligosaccharide content of human milk. J Pediatr Gastroenterol Nutr. 2017;64:789e98.
  23. Rueda-Cabrera R, Gil A. Nutrición en inmunidad en el estado de salud. In: Tratado de Nutrición; Editorial Médica Panamericana. Madrid, 2017; Vol. 4.
  24. Rumbo M, Schiffrin EJ. Ontogeny of intestinal epithelium immune functions: Developmental and environmental regulation. Cell Mol Life Sci. 2005;62:1288-96.
  25. Klose CS, Artis D. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat Immunol. 2016;17:765-74.
  26. Wang M, Li M, Wu S, et al. Fecal microbiota composition of breast-fed infantsis correlated with human milk oligosaccharides consumed. J Pediatr Gastroenterol Nutr. 2015;60:825.
  27. Nolan LS, Parks OB, Good M. A review of the immunomodulating components of maternal breast milk and protection against necrotizing enterocolitis. Nutrients. 2020;12:14.
  28. Sodhi CP, Wipf P, Yamaguchi Y, et al. The human milk oligosaccharides 2'-fucosyllactose and 6'-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Pediatr Res. 2021;89(1):91-101.
  29. Steenhout P, Sperisen P, Martin FP, et al. Term infantformula supplemented with human milk oligosaccharides (20-fucosyllactose and lacto-N-neotetraose) shiftsstool microbiota and metabolic signatures closer to that of breastfed infants. FASEB J. 2016;30:275-7.
  30. De Leoz MLA, Kalanetra KM, Bokulich NA, et al. Humanmilk glycomics and gut microbial genomics in infant feces show a correlation between human milk oligosaccharides and gutmicrobiota: A proof-of-concept study. J Proteome Res. 2015;14:491-502.
  31. Kirmiz N, Robinson RC, Shah IM, et al. Milk Glycans and Their Interaction with the Infant-Gut Microbiota. Annu Rev Food Sci Technol. 2018;9:429-50.
  32. Gotoh A, Katoh T, Sakanaka M, et al. Sharing of human milk oligosaccharides degradants within bifidobacterial communities in faecal cultures supplemented with Bifidobacterium bifidum. Sci Rep. 2018;8:1-14.
  33. Lawson MA, O’Neill IJ, Kujawska M, et al. Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a singlee cosystem. ISME J. 2019;14:635-48.
  34. Tonon KM, Morais TB, Taddei CR, et al. Gut microbiota comparison of vaginally and cesarean born infants exclusively breastfed by mothers secreting α1-2 fucosylated oligosaccharides in breast milk. PLoS One. 2021;16(2):e0246839. doi: 10.1371/journal.pone.0246839
  35. Newburg DS, Ruiz-Palacios GM, Morrow AL. Human milk glycans protect infants against enteric pathogens. Annu Rev Nutr. 2005;25:37-58.
  36. Laucirica DR, Triantis V, Schoemaker R, et al. Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells. J Nutr. 2017;147:1709-14.
  37. Newburg DS, He Y. Neonatal Gut Microbiota and Human Milk Glycans Cooperate to Attenuate Infection and Inflammation. Clin Obs Gynecol. 2015;58:814-26.
  38. Bode L. Human milk oligosaccharides in the prevention of necrotizing enterocolitis: A journey from in vitro and in vivo models to mother-infant cohort studies. Front Pediatr. 2018;6:385.
  39. Moossavi S, Sepehri S, Robertson B, et al. Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors. Cell Host Microbe. 2019;25:324-35.e4.
  40. Suzuki T, Yoshida S, Hara H. Physiological concentrations of short-chain fatty acids immediately suppress colonic epithelial permeability. Br J Nutr. 2008;100:297-305.
  41. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16:341-52.
  42. Zou Y, Wang J, Wang Y, et al. Protection of Galacto-Oligosaccharide against E. coli O157 Colonization through Enhancing Gut Barrier Function and Modulating Gut Microbiota. Foods. 2020;9(11):1710.
  43. Parada Venegas D, De la Fuente MK, Landskron G, et al. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019;10:277.
  44. Tian S, Wang J, Yu H, et al. Changes in Ileal Microbial Composition and Microbial Metabolism by an Early-Life Galacto-Oligosaccharides Intervention in a Neonatal Porcine Model. Nutrients. 2019;11(8):1753. doi: 10.3390/nu11081753; PMID: 31366090; PMCID: PMC6723927
  45. Vandenplas Y, Savino F. Probiotics and Prebiotics in Pediatrics: What Is New? Nutrients. 2019;11(2):431. doi: 10.3390/nu11020431; PMID: 30791429; PMCID: PMC6412752
  46. Walsh C, Lane JA, van Sinderen D, Hickey RM. Human milk oligosaccharides: shaping the infant gut microbiota and supporting health. J Funct Foods. 2020;72:104074. doi: 10.1016/j.jff.2020.104074
  47. Reverri EJ, Devitt AA, Kajzer JA, et al. Review of the Clinical Experiences of Feeding Infants Formula Containing the Human Milk Oligosaccharide 20-Fucosyllactose. Nutrients. 2018;10:1346.
  48. Akkerman R, Faas MM, de Vos P. Non-Digestible Carbohydrates in Infant Formula as Substitution for Human Milk Oligosaccharide Functions: Effects on Microbiota and Gut Maturation. Crit Rev Food Sci Nutr. 2019;59:1486-97.
  49. Arslanoglu S, Moro GE, Boehm G. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. J Nutr. 2007;137:2420-4.
  50. Puccio G, Alliet P, Cajozzo C, et al. Effects of infant formula with human milk oligosaccharides on growth and morbidity: A randomized multicenter trial. J Pediatr Nutr. 2017;64:624-31.
  51. Elison E, Vigsnaes LK, Rindom Krogsgaard L, et al. Oral supplementation of healthy adults with 2'-O-fucosyllactose and lactoN-neotetraose is well tolerated and shifts the intestinal microbiota. Br J Nutr. 2016;116:1356-68.
  52. Šuligoj T, Vigsnæs LK, Abbeele PVD, et al. Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function. Nutrients. 2020;12(9):2808. doi: 10.3390/nu12092808; PMID: 32933181; PMCID: PMC7551690
  53. Donovan SM, Comstock SS. Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity. Ann Nutr Metab. 2016;69(Suppl. 2):42-51.
  54. Guzmán-Rodríguez F, Alatorre-Santamaría S, Gómez-Ruiz L, et al. Employment of Fucosidases for the Synthesis of Fucosylated Oligosaccharides with Biological Potential. Biotechnol Appl Biochem. 2019;66:172-91.
  55. Román E, Moreno Villares JM, Domínguez Ortega F, et al. Real-world study in infants fed with an infant formula with two human milk oligosaccharides. Nutr Hosp. 2020;37(4):698-706.
  56. Bosheva M, Tokodi I, Krasnow A, et al. Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial. Front Nutr. Front Nutr. 2022;9:920362. doi: 10.3389/fnut.2022.920362; PMID: 35873420; PMCID: PMC9298649

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. The main breast milk oligosaccharides (BMOs) structures are shown in yellow and blue in the center of the figure. The top panel shows fucosylated BMOs and the bottom panel sialylated BMOs. The building blocks are shown at the very bottom of the figure [18].

Download (71KB)
Indexing metadata
3. Fig. 2. Major lymphocyte populations of gut-associated lymphoid tissue [19].

Download (247KB)
Indexing metadata
4. Fig. 3. Relative mRNA levels of inflammatory factors normalized by β-actin mRNA expression: A) inflammatory factors in the ileum; B) inflammatory factors in the colon. Different letters (a–c) are used to indicate significant differences (n<0.05) of the same factor among groups.

Download (61KB)
Indexing metadata

Copyright (c) 2022 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74329 от 19.11.2018 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies